Technological advances in nanodevice fabrication have expanded the capability to develop optical and electrical interfaces between man-made and biological materials. Nanostructured thin films fabricated from semiconductor nanoparticles show particular promise for interfacing cells with semiconductors because of their small size and because their optical, electronic and surface morphological features can be engineered to specific functions. Semiconductor nanostructured thin films are capable of generating robust photocurrents upon illumination as a result of ordered electron transport over the film surface, and this makes possible the coupling of photoactivation and electrical stimulation of neurons in close contact with the film. The ability to interface photoelectric materials with neurons could be an initial step in developing an active control interface between prostheses and the human body, and may eventually be used to engineer implants that could act as therapeutic devices or even serve as an artificial retina. One of the problems in developing a successful interface between neurons and thin films is attaining close contact while minimizing potentially toxic interaction of neurons and semiconductors. We propose to optimize the interface between NP thin films and neurons using surface modifications, primarily proteins and peptides that will enhance contact between the nanostructured thin films and neurons, and will increase the efficacy of photostimulation of neurons. Such surface modifications will also be used to engineer the optimum biocompatible interface between the thin film and neurons by decreasing direct contact with semiconductor material. Specifically our aims are to: (1) Engineer nanostructured thin-film cathodic and anodic photoelectrodes that have high photocurrent generation and have peptide or protein derivatives designed to increase adherence of neurons. (2) Demonstrate decreased contact distance and increased cell survival of neurons cultured on peptide- or protein-modified nanostructured thin films. (3) Show that increased coupling in the modified nanostructured thin films results in more efficient coupling of photostimulation and neuronal stimulation. These aims are designed to address the optimization of biocompatibility and functionality of the neuron-thin film interface. These findings might be of particular relevance in the application of semiconductors and other nanostructured materials to biomedicine.